Schisandrin C improved intestinal permeability through NF-ĸB and p38 MAPK mediated regulation of MLCK/MLC/tight junction signaling pathway

Title
Schisandrin C improved intestinal permeability through NF-ĸB and p38 MAPK mediated regulation of MLCK/MLC/tight junction signaling pathway
Authors
이희주강경수김주연김미리응우엔 트란 투 유엔하 민 응옥김정호
Issue Date
2021-08
Publisher
2021 International Symposium and Annual Meeting of the KSABC
Abstract
Inflammatory bowel disease (IBD) is associated with a variety of factors including increased intestinal permeability, disruption of intercellular junction proteins, and abnormal immune responses by harmful gut microbes. The purpose of this study is to evaluate the effect of schisandrin C on intestinal cell inflammation, and intestinal permeability dysfunction in cultured human intestinal cells and impaired gut barrier of C. elegans. Schisandrin C is selected through an anti-inflammatory screening in HT-29 cells among compounds isolated from S. chinensis. Schisandrin C improved transepithelial electrical resistance (TEER) and intestinal permeability which are destroyed by IL-1β, a pro-inflammatory cytokine in Caco-2 cells. In addition, the effect of schisandrin C on tight junction (TJ) proteins was investigated by western blot analysis and fluorescence microscopy. FITC-dextran permeability in the intestine of nematode C. elegans was also measured to access the protective effect of schisandrin C against P. aeruginosa, a intestinal permeability-dysfunction inducer. Schisandrin C significantly increased ZO-1 protein expression in Caco-2 cells, which was severely decreased by the IL-1β treatment. Schisandrin C also restored long MLCK and p-MLC protein expression, which is significantly increased by IL-1β. Schisandrin C inhibited NF-ĸB, p38 MAPK signaling Caco-2 cells and ameliorated the intestinal permeability of C. elegans damaged by P. aeruginosa. In summary, schisandrin C significantly improves intestinal permeability by regulating the expression of TJ, long MLCK, p-MLC, and inflammation-related proteins which are closely related to the IBD development in vitro. Additionally, schisandrin C also restored the intestinal permeability of C. elegans in vivo. Therefore, schisandrin C may serve as a promising chemical for the prevention and treatment of IBD.
URI
http://pubs.kist.re.kr/handle/201004/73749
ISSN
-
Appears in Collections:
KIST Publication > Conference Paper
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